The peripheral vasculature is controlled by neural, humoral, and intrinsic or local regulatory mechanisms; the intrinsic mechanisms are concerned with balancing vascular exchange capacity with the needs of the tissues. The objective of this research is to develop a view of the quantitative relations between tissue demands and vascular supply, with special reference to the supply and consumption of oxygen. We are interested in describing,by direct observation of the microcirculation, which microcirculatory elements are involved in regulation and their relative importance. In addition, we wish to determine how controls of the arteriolar diameter, capillary density, and red blood cell concentration are integrated. Finally, we wish to ascertain how the biochemical feedback between parenchymal cells and microvascular elements is accomplished and to evaluate the possible roles of oxygen and adenosine in this process. Specific proposals involve the following measurements and questions: 1. Is tissue PO2 a parameter which is tightly regulated by local control mechanisms, or is it a dependent variable reflecting the sum of a number of processes? 2. Is the capillary flow distribution regulated to assure homogeneous perfusion, and is the end capillary oxygen tension accurately reflected by the venous oxygen tension? 3. What is the range of sensitivity of the vascular smooth muscle muscle cells to oxygen, and is in this range compatible with a role for oxygen in regulation? 4. Is accelerated adenosine deamination an effective method of blocking functional hyperemia or the microvascular response to oxygen?